Enhancing HIV positivity yield in southern Mozambique: The effect of a Ministry of Health training module in targeted provider-initiated testing and counselling

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers’ training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module (“observation phases”). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions (“routine phases”). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11–2.14). Age (25–49 years) (OR = 2.43; 95%CI: 1.37–4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17–11.23), unawareness of partner’s HIV status (OR = 2.50; 95%CI: 1.91–3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03–2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.

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If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent.If patients provided informed written consent to have data from their medical records used in research, please include this information.RE: Thank you for the feedback on the Ethics statement and participant consent details.
We have revised and updated the Ethics statement in the Methods section (line 230), addressing the approach for both observation and routine study phases: "All study participants, both healthcare providers and individuals presenting at the healthcare facilities during the observation phases of the study, completed written IC.For participants aged 15-18 years, a parent/legal representative's additional consent was necessary.Regarding the routine phases, as we extracted de-identified aggregated data, informed consent was not required".Should there be a necessity for further clarification or additional information on participant consent, we are prepared to provide any necessary details as guided by your instructions.Executive Agency and EU are not responsible for any use that may be made of the information it contains).SW, employed by CDC participated in the conceptualization, study design and manuscript revision.For the remaining authors none were declared.

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The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the funding agencies." Please include your amended statements within your cover letter; we will change the online submission form on your behalf.RE: We appreciate the guidance on the appropriate placement of funding information in our manuscript.The funding acknowledgement mentioned in this sentence "We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/ 10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Programme", is not directly associated with the funding for this study.Our institution requires us to include this information in the acknowledgements.However, as requested by the editor, we have removed it from the manuscript and reallocated it at the end of the funding statement.
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Review Comments to the Author
The study brings a very important message in reaching the last mile of the first 95% UNAIDS target, particularly for Mozambique where the HIV burden is still high.
However, as a general comment I think the generalizability of the study results is compromised first because the study was limited to a single geographical area in Mozambique (Mozambique is a sizeable country with a lot of diversity, even within the health sector).Second, the study did not include a control group which would have allowed for a more meaningful comparison.Finally, I think if the study had been conducted over a long period of time, one could have been able to assess long term trends and more accurate predictions.
However, I applaud the investigators as despite the limitations the study raises some important points for programs to consider: 1) if the current algorithms are still adequate for the last mile, 2) the current training is it enough, frequency, quality and 3) application of evidence based strategies.For this I believe this article is very important.RE: Thank you for the comprehensive overview and recognizing the study's importance in shaping HIV programs toward achieving the last mile of the first 95 UNAIDS target.
We acknowledge that the absence of a control group may impact the ability of draw causal inferences.This limitation has been appropriately addressed and discussed in the manuscript's Discussion section at line 482.Regarding the duration of the study, as our analysis did not focus on trends, this factor did not impact our findings.However, as this is a first step, we recognize the importance of conducting a longer-term study to analyse future trends.
Concerning the study's restriction to a rural setting, we acknowledge the reviewer's point about potential limitations in generalizing the results to urban areas.However, as elaborated further in a subsequent comment, our intentional focus was on a rural area marked by a significant HIV burden and constrained resources Some few comments: - -The study was conducted in a rural area in Maputo province.Could the authors explain the choice of the health facilities?Why were some urban health facilities in Maputo not included?RE: Thank you for the insightful comment.The authors chose to focus the study on a semi-rural area due to its high HIV prevalence and the strain on its healthcare system, which operates with limited resources.These details have been included in the Methods section at line 134.Our aim was to contribute insights into rural areas, often overshadowed by urban areas, despite their crucial role in the "last mile" efforts targeting harder-to-reach populations.We have made specific modifications throughout the manuscript (lines 51, 71, 123, 385, 431 and 501) to emphasize that our study setting and findings are centred on rural areas.Additionally, our team has established a longstanding collaboration with the local HIV program implementer, Fundação Ariel, which significantly supported our research efforts in this area.The selection of the healthcare facilities within the study area was based on patient volume, including the four highestvolume facilities in the district (line 132).Acknowledging Mozambique's diverse healthcare landscape, as highlighted by the reviewer in the overview, we recognize that our specific site selection might limit generalizability to urban areas.However, given our study's focus on rural challenges, the authors do not consider this a limitation and believe our findings hold potential applicability to other rural areas facing similar challenges of a high HIV burden and constrained resources.

-Could the authors please specify the professional level of the health professionals in the triage and emergency department areas? Could this have influenced in the results for example if some facilities had doctors vs nurses in triage?
RE: We appreciate the comment.All 19 healthcare providers included in the study were medical assistants (line 235), who, in Mozambique, undergo four years training in basic medical care, allowing them to prescribe medicines and support minor surgeries.This uniform professional level minimised the potential influence of professional level diversity in our analysis.However, as the reviewer infers, if the training were applied to healthcare workers with variations in professional levels, the impact of training on HIV testing yield could differ based on the pre-training experience and background of individuals.We have included this important observation in the Discussion section at line 493.It is important to note that HIV testing referral tasks in Mozambique are primarily carried out by medical assistants and nurses.
-Line 417 -included references twice, please delete one RE: Thank you for highlighting the error.We have now removed the duplicated references as per your observation.

Global overview
This is an interesting study measuring the effectiveness of a training module to improve the yield of PITC in triage and emergency departments using a pre-post study design.
While acknowledging the significance of the study, I find that the manuscript lacks focus and requires a more cautious interpretation of some results.
Since their main objective is to enhance "positivity yield" (i.e., the sensitivity of the screening algorithm), I do believe they should consider the volume of new positive cases in the assessment.I understand that we want to improve the yield to reduce time burden and cost of doing systematic test but this should not be at the expense of the volume of newly diagnosed individuals (e.g., for a same denominator, it is better to have a yield of 5% if it leads to 100 new cases of HIV positivity rather than a yield of 10% and only 10 new cases of HIV positivity).Usually, this information would be given by sensibility (which would have provided the number of true HIV negative excluded), but the current study design does not allow to infer on that aspect.Thus, I believe this is important to provide alongside those yields, the number of new cases with the number of eligible population (e.g., patient seen in emergency services).
The authors have included a secondary objective which aims to improve the current PITC algorithm.I am not comfortable with that analysis as I have some doubts about the generalization of their results.There is not much description for the methods of that secondary objective especially on how the 509 positives tests have been included in the analysis (during the intervention, before or both?), and the fact that this population has within the total positives.In the pre-training observation phase, sensitivity was 92% (269/291); 95%CI: 89-95%, and in the post-training observation phase, it reached 95% (207/218); 95%CI: 91-97%.For the routine phases, reliance on real-world daily testing data without implementing universal testing made it unfeasible to estimate sensitivity due to the unknown total number of HIV positives.Considering these limitations, we opted not to include the sensitivity values in the manuscript.
We have also revised our manuscript to enhance clarity regarding the secondary objective (lines 47, 125 and 217), which aimed to evaluate factors associated with a positive HIV test, following similar methodologies used in other studies such as Abdul et al, 2023.This analysis involved all 509 individuals who tested positive during both observation phases (line 331).Throughout these phases, we collected data on sociodemographic characteristics, signs, symptoms and risk factors suggestive of HIV.These individuals represent all the positive individuals among those who visited the healthcare facilities during the observation phases.In our study, additional HIV study counsellors conducted tests for all individuals without a known HIV diagnosis, regardless of whether they were referred through PITC by healthcare providers (lines 196).This way, we minimised the risk of selection bias.
Lastly, we agree with the reviewer's point referring to the fact that our methodology did not directly evaluate the improvement of the current PITC algorithm.Consequently, we have rephrased the section where we discussed the optimisation of the current PITC algorithm to avoid any confusion regarding our study's objectives (line 367).We explicitly clarified that the 2.6% increase in new diagnoses by including new factors, and the 3.5% increase by removing the recent-HIV negative test exclusion criteria were observed within our study population (lines 65-68, 379, 392 and 456-470).The significance of these findings lies in their potential to guide further studies in evaluating the performance of the targeted PITC algorithm following these potential adaptations.We appreciate the reviewer's interest in illustrating the monthly evolution of HIV test positivity.However, our study design was not tailored for time series analysis or trend evaluation.Due to the limited number of time points and the small sample size per point, the validity of conducting a valid time series analysis, such as an interrupted time series analysis, could be compromised.As previously mentioned to reviewer 1, our study marks an initial step, and we fully acknowledge the need for a longer-term study to analyse future trends.Additionally, considering the difficulty in interpreting the yield alone (it should be reported along with the numerator and denominator, as also suggested by the reviewer), we do not consider yield as an appropriate outcome for time series analysis.
Regarding the lower number of individuals observed during the observation phases compared to the routine phases, several factors might explain this difference: -We excluded unaccompanied individuals under 18 and non-residents of Manhiça district (line 152).A prior study in the same area (Fuente-Soro et al, 2018) found that 36% of positive cases involved individuals not residing in the district, potentially seeking testing in other districts due to stigma.
-During the observation phases, we recruited individuals attending the healthcare facility from 8 AM to 3 PM, Monday to Friday.In contrast, for the routine phases, we extracted aggregated data from data collection books that included all individuals accessing healthcare facilities round the clock, including weekends and bank holidays.It was not feasible to disaggregate the data by day or time.
-Approximately 18% of healthcare providers across the four facilities declined participation, primarily because their usual working hours did not align with the study hours (from 8 AM to 3 PM) or because they occasionally worked in the triage/ED but it was not their regular duty (line 148).
-Lastly, the conclusions (line 499) have been revised to accurately reflect the implications drawn from our study findings.
Section of your manuscript: "We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/ 10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Programme.The authors gratefully acknowledge the staff at Centro de Investigação em Saúde de Manhiça, in the Manhiça District, Mozambique, who worked to collect and manage the data, the Ministry of Health of Mozambique, our research team, collaborators, and especially all communities and participants involved."We note that you have provided funding information that is not currently declared in your Funding Statement.However, funding information should not appear in the Acknowledgments section or other areas of your manuscript.We will only publish funding information present in the Funding Statement section of the online submission form.Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement.Currently, your Funding Statement reads as follows: "This publication has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of NU2GGH002092, the Severo Ochoa predoctoral fellowship by the Barcelona Institute of Global Health (ISGlobal) to ASL, the predoctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and cofounded by European Social Fund to ASL and SFL, and the European Respiratory Society (ERS) and the European Union (EU)'s H2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement [847462] to ELV (This publication reflects only the author's view.The ERS, Research supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of NU2GGH002092, the Severo Ochoa predoctoral fellowship by the Barcelona Institute of Global Health (ISGlobal) to ASL, the predoctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and cofounded by European Social Fund to ASL and SFL, and the European Respiratory Society (ERS) and the European Union (EU)'s H2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement [847462] to ELV (This publication reflects only the author's view.The ERS, Research Executive Agency and EU are not responsible for any use that may be made of the information it contains).SW, employed by CDC participated in the conceptualization, study design and manuscript revision.For the remaining authors none were declared.The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the funding agencies.Lastly, we acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/ 10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Programme." Was the training online or was it in person, what was the duration of the training and how many health professionals were trained?RE: Thank you for the comment.The training sessions covering signs, symptoms, and risk factors for HIV (targeted PITC) were conducted in person by the HIV testing and counselling reference group from the Mozambican Ministry of Health at the Manhiça District hospital.These details have been added in line 183 of the manuscript.The training spanned one week, from the 13 th to the 19 th of May (refer to Figure 1 for clarification).The 19 healthcare professionals who participated in the study were the same individuals who attended this training module, as mentioned in lines 149 and 235, having agreed to take part in both study phases and the training.

TitleRE:
Figure 2 resolution is very low, I was not able to read it.It would have been interesting to have a figure should the evolution of those positive yield per month or every two months to see the eventual fluctuation of positivity yield.I am not certain to understand the drop of patients seen during the study period (n=7,102, ~1776 patients seen per month) compared to the routine period (n=33,261, ~ 4,158 per month).